Transmitter release at the hair cell ribbon synapse

Single auditory nerve fibers in the cat were labeled intracellularly with horseradish peroxidase. The sample of fibers was selected to represent different response types over a wide range of characteristic frequencies. All 56 labeled neurons were found to be radial fibers innervating inner hair cells, suggesting that none of the single-unit data reported to date has been from the outer hair cell innervation. Differences in rates of spontaneous discharge and thresholds to tones among these labeled neurons were closely correlated with morphological differences in the caliber and location of their unmyelinated terminals on the body of the inner hair cell.

Excitable cells use ion channels to tailor their biophysical properties to the functional demands made upon them. During development, these demands may alter considerably, often associated with a change in the cells' complement of ion channels. Here we present evidence for such a change in inner hair cells, the primary sensory receptors in the mammalian cochlea. In mice, responses to sound can first be recorded from the auditory nerve and observed behaviourally from 10-12 days after birth; these responses mature rapidly over the next 4 days. Before this time, mouse inner hair cells have slow voltage responses and fire spontaneous and evoked action potentials. During development of auditory responsiveness a large, fast potassium conductance is expressed, greatly speeding up the membrane time constant and preventing action potentials. This change in potassium channel expression turns the inner hair cell from a regenerative, spiking pacemaker into a high-frequency signal transducer.

Efferent feedback onto sensory organs provides a means to modulate input to the central nervous system. In the developing mammalian cochlea, inner hair cells are transiently innervated by efferent fibers, even before sensory function begins. Here, we show that neonatal inner hair cells are inhibited by cholinergic synaptic input before the onset of hearing. The synaptic currents, as well as the inner hair cell's response to acetylcholine, are mediated by a nicotinic (alpha9-containing) receptor and result in the activation of small-conductance calcium-dependent potassium channels.